Would You Believe 70,000 Genes?

March 17, 2002

New evidence suggests that humans may have about 70,000 genes instead
of the 30,000 to 40,000 genes previously announced by the Human Genome
Project:

BOSTON--The annual meeting of the American Association for the
Advancement of Science (publisher of Science), held from 15 to 19
February, included symposia across the scientific
disciplines. According to one presentation, the number of human genes
may actually be much closer to the early prediction of 70,000 genes
rather than the much smaller number predicted when the draft sequence
was published last year. ...

When the draft human genome sequence was completed last year, a
computer analysis suggested that the number of genes was shockingly
small. Now, an experimental approach suggests that the number may
actually be much closer to the early prediction of 70,000 genes,
according to a presentation on 16 February.

...

Later in the day, Victor Velculescu mounted a small rebellion by
raising the gene count. He and his colleagues, at Johns Hopkins
University in Baltimore, Maryland, have gone back to the lab to look
for genes that the computer programs may have missed. Their technique,
called serial analysis of gene expression (SAGE), works by tracking
RNA molecules back to their DNA sources. After isolating RNA from
various human tissues, the researchers copy it into DNA, from which
they cut out a kind of genetic bar code of 10 to 20 base pairs. The
vast majority of these tags are unique to a single gene. The tags can
then be compared to the human genome to find out if they match up with
genes discovered by the computer algorithms. Velculescu said that
only roughly half of the tags match the genes identified
earlier--evidence, he says, that the human inventory of genes had been
underestimated by about half.

The reason for the disparity may be that the standard computer
programs were largely developed for the genomes of simple
(prokaryotic) organisms, not for the more complex sequences found in
the genomes of humans and other eukaryotes. "We're still not very
good at predicting genes in eukaryotes," said Claire Fraser of The
Institute for Genomic Research in Rockville, Maryland. It's entirely
possible that there could be more than 32,000 genes, and SAGE is an
important approach to finding them, she says: "You absolutely have to
go back into the lab and get away from the computer terminal."

So even with the human genome sequenced, we still don't know how many
genes we have. And yet we are sure that humans evolved from lower
organisms! Perhaps more humility would be appropriate. Furthermore,
if the genomes of humans and other eukaryotes are so much different
than those of prokaryotes, this could also pose a problem for the
theory of evolution, namely, how these more complex genetic mechanisms
evolved. In addition, there could be even more than 70,000 genes,
because some genes may be only rarely expressed, and would not be
detected by the SAGE technique.